Practical aziridinations II: Electronic modifications to poly(pyrazolyl)borate-copper catalysts

Article abstract of DOI:10.1016/j.tetlet.2006.01.016

A significant influence of the electronic features of poly(pyrazolyl)borate ligands on the efficiency of the copper-catalyzed aziridination reaction has been noted. Electron-deficient, bidentate di(pyrazolyl)borates in conjunction with copper(II) chloride

Full text of DOI:10.1016/j.tetlet.2006.01.016

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1821–1823
Practical aziridinations II: electronic modifications
to poly(pyrazolyl)borate–copper catalysts
*
Scott T. Handy, Anatole Ivanow and Mark Czopp
Department of Chemistry, State University of New York at Binghamton, Binghamton, NY 13902, USA
Received 28 November 2005; accepted 5 January 2006
Available online 24 January 2006
Abstract—A significant influence of the electronic features of poly(pyrazolyl)borate ligands on the efficiency of the copper-catalyzed
aziridination reaction has been noted. Electron-deficient, bidentate di(pyrazolyl)borates in conjunction with copper(II) chloride gen-
erated the most effective catalyst system for the aziridination of a variety of olefins.
Ó 2006 Published by Elsevier Ltd.
As part of an ongoing interest in practical, simple, cata-
lytic methods for the preparation of organic building
blocks, we have been particularly attracted to the chal-
lenge of preparing aziridines. The most straightforward
synthetic strategy is the cycloaddition of an olefin with a
Part of the difficulty in solving these limitations is the
limited (and frequently conflicting) mechanistic infor-
mation regarding the metal-catalyzed aziridination reac-
5
tion. The other major limitation is that most currently
employed catalyst systems are not readily tunable. Thus,
factors such as steric and electronic effects can only be
studied with great difficulty.
1
nitrogen source, which parallels the most common
methods of preparing epoxides (using peracids or perox-
ides) and cyclopropanes (using carbenes or carbenoids).
Unlike the carbon and oxygen systems, though, this
Our approach to this problem is to employ poly(pyraz-
olyl)borate–copper complexes as the aziridination cata-
[
2+1] route to aziridines remains problematic. The obvi-
6
,7
ous nitrogen source for these reactions, a nitrene, is
extremely reactive and will undergo a variety of reac-
tions beyond simple aziridination. Although similar
difficulties with the use of carbenes have been largely re-
lyst.
The simplicity of preparing a wide range of
modified poly(pyrazolyl)borate ligands combined with
the stability of these species lends itself to the develop-
8
ment of a practical, versatile catalytic system. Indeed,
2
solved by the use of metal catalysts, the same approach
we have already reported the use of in situ generated
TP and DP complexes with copper as effective aziridin-
toward control of nitrene reactivity has not progressed
to a synthetically advanced state.
7
ation catalysts. By tuning the hapticity of the ligand
and the starting oxidation state of copper, a catalyst sys-
tem was generated that was effective for the azidination
of a variety of aryl-substituted olefins (Fig. 1). Unfortu-
nately, the yields for aliphatic olefins remained low.
This is not due to a lack of effort. A considerable num-
ber of catalyst systems have been reported, but they all
have significant limitations. One common issue is the
3
relatively high catalyst loadings that are required
4
(
>5 mol %) to achieve optimal yields. Another problem
These initial studies made use of some of the flexibility
afforded by the poly(pyrazolyl)borate skeleton. How-
ever, beyond the ability to vary the hapticity of the
ligand, the poly(pyrazolyl)borates afford the oppor-
tunity to optimize the electronic effects of the ligand
on the azidirination reaction. In particular, it seemed
logical that less electron-rich poly(pyrazolyl)borate
catalysts could be more active, since these species
should be more Lewis acidic and thus better able to
coordinate with the nitrene precursor and/or the olefin.
Indeed, Dias and co-workers have observed that the
is that reaction yields are good for aryl-substituted ole-
fins (such as styrene), but are unacceptably low for sim-
ple aliphatic olefins (such as cyclooctene).
Keywords: Catalysis; Cycloaddition; Copper; Ligands; Substituent
effects; Aziridines.
*
Corresponding author at present address: Department of Chemistry,
Middle Tennessee State University, Murfreesboro, TN 37130, USA.
Tel.: +1 615 494 8655; fax: +1 615 898 5182; e-mail:
shandy@mtsu.edu
0040-4039/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.01.016

1822
S. T. Handy et al. / Tetrahedron Letters 47 (2006) 1821–1823
(Table 2).11 Only in the case of 1,2-disubstituted olefins
Ts
N
PhI=NTs
was a significant difference noted. Thus, both b-methyl-
styrene and dihydronaphthalene afforded much higher
yields using the electron-deficient catalyst system than
Ph
DP*Na/CuCl2
Ph
CH CN
3
*
16 h, 89%
with the electron-rich DP Na/CuCl catalyst (entries 3
2
Ts
and 4).
N
PhI=NTs
A greater challenge is faced in the aziridination of alkyl-
F
*
DP*Na/CuCl2
substituted olefins. Application of the same DP Na/
CuCl2 reaction conditions afforded good to modest
CH CN
3
16 h, 36%
11
results for some simple olefins (Table 3). Somewhat
*
more strained olefins (pinene and cyclooctene) afforded
higher isolated yields (50% and 63%, respectively), while
a simple monosubstituted olefin (1-octene) afforded the
lowest yield (20%). It is worth noting that in no case
was any allylic amination product detected, even with
cyclohexene, which is particularly prone to this mode
Figure 1. Aziridinations with in situ generated DP CuCl.
F*
tris[3,5-bis(trifluoromethyl)pyrazolyl]borate (TP ) li-
gand, in combination with metals such as copper, zinc,
or silver, forms stable complexes with a variety of donor
9
12
ligands including THF, DMF, and DMAC.
of reactivity.
Based on this precedent, the necessary DP and TP li-
gands were prepared using the standard literature proce-
a
1
0
Table 2. Aziridination of aryl-substituted olefins
dures. With these ligands in hand, their catalytic
efficiency in the aziridination of cyclooctene was investi-
gated (Table 1). As had been observed previously with
b
Entry
Olefin
Product
Yield (%)
Ts
N
*
*
styrene and the DP and TP systems, there was a small,
but significant, effect of matching the ligand hapticity
and the starting copper oxidation state (entries 1–4).
This effect was also observed for the electron deficient
poly(pyrazolyl)borate ligands (entries 5–8). More
importantly, however, by matching the hapticity and
oxidation state with the electron-deficient ligands, a sig-
nificant improvement in the aziridination yield was
1
90
Ph
Ph
Ts
N
2
3
4
94
Ph
Ph
Ph
Ts
N
c
64 (46)
F
*
observed. Thus, with the DP Cu(II) Cl catalyst, the
aziridination product of cyclooctene was isolated in
Ph
6
3% yield.
NTs
c
96 (56)
F
*
Armed with this promising observation, the DP Na/
CuCl conditions were applied to other olefins. Aryl-
2
a
All reactions were carried out on a 1 mmol scale using 10 mol % of
sodium bis[3,5-bis(trifluoromethyl)pyrazolyl]borate, 10 mol % of
copper(II) chloride, and 5 equiv of olefin in 2.7 mL of argon-purged
substituted olefins generally afford good results with
*
even the simple TP Na/CuCl catalyst, and equally good
F*
results were obtained using the DP Na/CuCl system
2
CH CN at rt.
3
b
c
Isolated yield (average of three reactions).
*
Performed using DP Na and CuCl
2
as the catalyst.
a
Table 1. Aziridination studies on cyclooctene
Ts
N
a
Table 3. Aziridination of alkyl-substituted olefins
PhI=NTs
catalyst
b
Entry
Olefin
Product
NTs
Yield (%)
CH CN, 16 h
3
1
28
50
b
Entry
Catalyst
Yield (%)
*
1
2
3
4
5
6
7
8
TP Na/CuCl
44
24
30
36
43
55
37
63
NTs
*
2
3
TP Na/CuCl
2
*
DP Na/CuCl
*
DP Na/CuCl
2
Ts
N
F
TP *Na/CuCl
F
20
TP Na/CuCl
2
Hexyl
*
F
DP *Na/CuCl
DP *Na/CuCl
Hexyl
F
2
a
All reactions were carried out on a 1 mmol scale using 10 mol % of
sodium bis[3,5-bis(trifluoromethyl)pyrazolyl]borate, 10 mol % of
copper(II) chloride, and 5 equiv of olefin in 2.7 mL of argon-purged
a
All reactions were carried out on a 1 mmol scale using 10 mol % of
the polypyrazolylborate salt, 10 mol % of copper chloride, and
5
equiv of olefin in 2.7 mL of argon-purged CH
3
CN at rt.
CH
3
CN at rt.
b
b
Isolated yield (average of three reactions).
Isolated yield (average of three reactions).

S. T. Handy et al. / Tetrahedron Letters 47 (2006) 1821–1823
1823
It certainly merits attention that even better results have
been reported using isolated tri(pyrazolyl)borate cop-
2. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds:
From Cyclopropanes to Ylides; John Wiley & Sons: New
York, 1998.
1
3
per(I) catalysts. Thus, Dias has reported that the azir-
idination of cyclohexene with 5 mol % of the ethylene
complex of copper(I) tris[3,5-bis(trifluoromethyl)pyraz-
olyl]borate affords the aziridination product in 93%
yield. Interestingly, for 1-octene, their results are very
similar to those obtained by us using the in situ gener-
ated catalyst (28% and 20%, respectively). Perez and
co-workers have also used an isolated copper cata-
lyst—copper(I) tris(2,3,4-tribromopyrazolyl)borate. At
a 5 mol % loading, this system afforded very good yields,
including a 91% yield for the aziridination of 1-hexene.
As a result, these isolated catalysts appear to afford bet-
ter results than our in situ generated catalysts, but they
do require the preparation and isolation of the catalysts,
which renders them a bit less convenient than our
method.
3
. For examples of catalysts used in aziridinations, see:
Copper) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J.
(
Am. Chem. Soc. 1994, 116, 2742; Li, Z.; Conser, K. R.;
Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326; Vyas,
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Tetrahedron Lett. 1998, 39, 309; (Rhodium) Albone, D. P.;
Aujla, P. S.; Taylor, P. C. J. Org. Chem. 1998, 63, 9569;
Mueller, P.; Baud, C.; Jacquier, Y. Can. J. Chem. 1998, 76,
7
1
38; Guthilonda, K.; DuBois, J. J. Am. Chem. Soc. 2002,
24, 13672; (Iron and Manganese) Mansuy, D.; Mahy, J.-
P.; Dureault, A.; Bedi, G.; Battieoni, P. J. Chem. Soc.,
Chem. Commun. 1994, 1161; Simanot, J.-P.; Pecaut, J.;
Scheidt, W. R.; Marchon, J.-C. Chem. Commun. 1999,
9
1
89; (Silver) Cui, Y.; He, C. J. Am. Chem. Soc. 2003, 125,
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4
. Halfen, J. A.; Hallman, J. K.; Schultz, J. A.; Emerson, J. P.
In conclusion, utilizing the facile tunability of the
poly(pyrazolyl)borate framework, we have discovered
a new class of aziridination catalysts that employ less
electron-rich ligands on the copper center. These cata-
lysts are readily generated in situ from stable precursors
and afford modest to excellent yields of the aziridine
products from both aryl and alkyl-substituted olefins.
Efforts are underway to develop a mechanistic under-
standing of the source of this enhanced activity as well
as the combined influence of the ligand hapticity and
the starting copper oxidation state. These efforts will
be reported in due course.
Organometallics 1999, 18, 5435.
5. For selected mechanistic studies, see: Evans, D. A.; Faul,
M. M.; Bilodeau, M. T. J. Am. Chem. Soc. 1994, 116,
2
742; Diaz-Requejo, M. M.; Perez, P. J.; Brookhart, M.;
Templeton, J. L. Organometallics 1997, 16, 4399; Li, Z.;
Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc 1995, 117,
5
1
889; Mueller, P.; Baud, C.; Jacquier, Y. Can. J. Chem.
998, 76, 738; Brandt, P.; Soedergren, M. J.; Andersson, P.
G.; Norrby, P.-O. J. Am. Chem. Soc. 2000, 122, 261.
. Perez, P. J.; Brookhart, M.; Templeton, J. L. Organomet-
allics 1993, 12, 261.
7. Handy, S. T.; Czopp, M. Org. Lett. 2001, 3, 1423.
8. For a review of poly(pyrazolyl)borates in general, see:
Trofimenko, S. Scorpionates: The Coordination Chemistry
of Polypyrazolylborate Ligands; Imperial College Press:
London, 1999.
6
Acknowledgements
9
. Dias, N. V. R.; Polach, S. A.; Coh, S.-K.; Archibong, E.
F.; Marynick, D. S. Inorg. Chem. 2000, 39, 3894, and
references sited therein.
The authors thank the State University of New York
and the Research Foundation for financial support of
this research.
*
*
10. TP and DP : Trofimenko, S. J. Am. Chem. Soc. 1967, 78,
*
F
3
170; TP : Renn, O.; Venanzi, L. M.; Marteletti, A.;
F
*
Gramlich, V. Helv. Chim. Acta 1995, 78, 993; DP : Dias,
H. V. R.; Gorden, J. D. Inorg. Chem. 1996, 35, 318.
1. All compounds exhibited spectral data identical to that
reported in the literature.
1
1
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